List of Principal Investigators Investigator Name Colón, Dr. Gildred Ortíz-Carrasquillo, Dr. Ramón Figueroa Cruz, Dr. Wanda Arakaki, Dr. Richard Liljenquist, Dr. David Klaff, Dr. Leslie Wynne, Dr. Alan Bode, Dr. Bruce Levin, Dr. Philip Rosenstock, Dr. Julio Bergenstal, Dr. Richard Roberts, Dr. Anthony Gerstman, Dr. Murray Davis, Dr. Tim Linjawi, Dr. Sultan Dudas, Dr. Mihaly Vandorfi, Dr. Gyozo Kis-Gombos, Dr. Piroska Jakubowska, Dr. Iwona Szyprowska, Dr. Ewa Pintilei, Dr. Ella Ciomos, Dr. Daniela Guja, Dr. Cristian Veresiu, Dr. Ioan Arefieva, Dr. Elena Ivanova, Dr. Svetlana Pavlova, Dr. Maria Vorobiev, Dr. Sergey De Teresa Parreño, Dr. Luis Durán García, Dr. Santiago Tinahones Madueño, Dr. Francisco Site Name and Country American Telemedicine Center, San Juan Health Center, Puerto Rico Manatí Medical Center, Puerto Rico Pradnet, Inc., Centro Especializado de Nutrición y Bariatría, Puerto Rico University of Hawaii, USA Rocky Mountain Diabetes and Osteoporosis Center, USA Rainier Clinical Research Center, USA Cotton O Neil Diabetes and Endocrinology Center, USA Atlanta Diabetes Associates, USA Model Clinical Research, USA Dallas Diabetes Endocrine Center, USA International Diabetes Center, USA SA Endocrine Research Pty Ltd, Australia Eastern Clinical Research Unit Maroondah Hospital, Australia Fremantle Hospital, School of Medicine and Pharmacology, Australia Coffs Endocrine and Diabetes Services, Australia Bekes Megyei Pandy Kalman Korhaz, Hungary Veszprem Megyei Csolnoky Ferenc Korhaz, Hungary XIII.ker Onkormanyzat Egeszsegugyi Szolgalat, Hungary I Oddz. Diabetologii, Endokrynologii i Chorob Wewnetrznych, Poland NZOZ CenterMed Lublin, Poland SC Consultmed SRL, Romania Cosamext SRL-Centrul Medical Puls, Romania Institutul National de Diabet Nutritie si Boli Metabolice, Romania Spitalul Clinic Judetean de Urgenta Cluj-Napoca, Romania Clinic of St. Elizabeth, Russia Arkhangelsk Regional Clinical Hospital, Russia Moscow Medical Academy, Russia Rostov State Medical University, Russia Clínica Mediterránea de Neurociencias, Spain Hospital Universitario Nuestra Señora de Valme, Unidad de Diabetes Consultas Externas, Spain Centro Especialidades San José Obrero (Barbarela), Hospital Virgen de la Victoria de Malagá España, Spain
Supplementary Table 1. LY1 and LY2 Measures of Glycemia at Week 12 LY1 LY2 GL (n=98) (n=97) (n=93) FBG (SMBG), mg/dl Mean 121.4 ± 3.1 115.1 ± 2.7 116.9 ± 2.7 LS Mean Diff a 5.8 0.2 -- 90% CI -1.6, 13.2-7.0, 7.4 -- p-value 0.194 0.956 -- FSG (Lab), mg/dl Mean 128.8 ± 4.1 117.1 ± 3.6 128.6 ± 4.1 LS Mean Diff a 0.4-9.2 -- 90% CI -8.8, 9.4-18.2, -0.4 -- p-value 0.959 0.090 -- Daily Mean BG, mg/dl Mean 143.6 ± 3.2 134.2 ± 2.9 144.7 ± 3.4 LS Mean Diff a 2.0-4.5 -- 90% CI -5.2. 9.2-11.7, 2.7 -- p-value 0.654 0.305 -- A1C, % Mean 7.1 ± 0.1 6.9 ± 0.1 7.2 ± 0.1 LS Mean Diff a 0.0-0.2 -- 90% CI -0.1, 0.2-0.3, -0.1 -- p-value 0.688 0.022 -- Body Weight, kg Mean 89.8 ± 1.9 91.0 ± 2.2 89.6 ± 2.1 LS Mean Diff -0.9-0.8 -- 90% CI -1.4, -0.4-1.2, -0.3 -- p-value 0.002 0.013 -- Total Hypoglycemia, events/30 d b Mean 1.37 ± 0.34 1.30 ± 0.33 1.52 ± 0.34 Ratio c 0.98 0.92 -- 90% CI 0.65, 1.47 0.61, 1.39 -- p-value 0.927 0.736 -- Nocturnal hypoglycemia, events/30 d b Mean 0.31 ± 0.11 0.19 ± 0.07 0.39 ± 0.12 Ratio c 0.87 0.52 -- 90% CI 0.50, 1.52 0.29, 0.92 -- p-value 0.686 0.059 -- Week 12 data are presented as raw mean ± SE. Treatment differences are reported as LS mean using mixed model repeated measures (MMRM). a LS mean treatment difference is for LY1 minus GL and LY2 minus GL, respectively. b Data reflect overall rate during 12 weeks of treatment. c Ratio is for LY/GL Abbreviations: A1C = hemoglobin A1C, BG = blood glucose, Diff = difference, FBG = fasting blood glucose, LY1 = LY2605541 algorithm 1 group, LY2 = LY2605541 algorithm 2 group, SE = standard error, SMBG = self-monitored blood glucose.
Supplementary Table 2. Change in Antibody Status to LY2605541 Baseline Week 12 Follow-up Increased Increased Combined LY2605541 (N=195) (n=150) (n=18) 158 (88.8%) 5 (2.8%) -- 151 (88.3%) 6 (3.5%) -- 2 (1.1%) 6 (3.4%) 7 (3.9%) 2 (1.2%) 12 (7.0%) 0 (0.0%) GL (N=93) (n=75) (n=9) 74 (87.1%) 2 (2.4%) -- 71 (86.6%) 2 (2.4%) -- 2 (2.4%) 6 (7.1%) 1 (1.2%) 2 (2.4%) 7 (8.5%) 0 (0.0%) Antibody status is categorized as negative and positive at baseline, 12 weeks (treatment period), and 16 weeks (follow-up period). Increased positive is defined as positive at baseline and percent binding is increased by at least 0.5%. The percent is calculated based on the total number of patients with antibody measurement for treatment and follow-up period respectively. Abbreviations: GL = insulin glargine.
Supplementary Figure 1. Study design.
Supplementary Figure 2. Patient disposition.
Supplementary Figure 3. Panel A shows the mean intra-day BG variability (in mg/dl) over the 12- week treatment period. Intra-day BG variability at a visit was quantified as the SD of 8-point SMBG profiles.. Panel B shows the mean inter-day BG variability (in mg/dl) over the 12-week treatment period. Inter-day SMBG variability at a visit was calculated as the SD of daily mean glucose. Solid line with closed circle = insulin glargine, dashed line with closed square = LY2605541. BG = blood glucose; SMBG = self-monitored blood glucose; SD = standard deviation. Solid line with closed circle = insulin glargine, dashed line with closed square = LY2605541. BG = blood glucose; SMBG = self-monitored blood glucose; SD = standard deviation.